| Résumé : | Introduction: Main metabolic causes of myopathies are fatty acid oxidation (FAO) deficiencies. LPIN1 defects have been involved in severe and early rhabdomyolysis. Lipin1 plays a dual role, as a phosphatidate phosphatase 1 (PAP1) and as a transcriptionnal coactivator of PPAR and PGC1 to regulate the expression of many genes, including those encoding FAO enzymes. The human Lipin family includes two other closely related members, Lipin 2 and 3, encoded by distinct genes. All three Lipin exhibit PAP1 activity and possess the LxxIL motif mediating interaction with nuclear factors.The aim of the study is to evaluate the prevalence of LPIN1, LPIN2 and LPIN3 mutations in a cohort of patients presenting with a wide spectrum of muscular diseases. Methods: 117 patients were recruited. Inclusion criteria were rhabdomyolysis bouts or exercice-induced muscular pains, in children or adults, after exclusion of FAO deficiency. The complete coding sequences of the three genes were analysed. Functional consequences of the substitutions were evaluated by a complementation test in the pah1 yeast strain. Results: We found 2 LPIN1 mutations in 22 patients (19%), 1 LPIN1 substitution in 1 patient, 1 LPIN2 substitution in 4 patients and 1 LPIN3 substitution in 4 patients. No patient was found with 2 mutations in LPIN2 or LPIN3.All patients with 2 LPIN1 mutations presented with severe (CPK > 10 000 UI/L) and early (first bout |
trié(s) par (Pertinence décroissant(e), Date de parution décroissant(e), Date de parution décroissant(e), Système de projection du document croissant(e)) Mettre toutes les notices dans le panier Faire une suggestion Ajouter un critère de recherche
